Proenkephalin

Proenkephalin (PENK), formerly known as proenkephalin A (since proenkephalin B was renamed prodynorphin), is an endogenous opioid polypeptide hormone which, via proteolyic cleavage, produces the enkephalin peptides met-enkephalin, and to a lesser extent, leu-enkephalin.^[5] Upon cleavage, each proenkephalin peptide results in the generation of four copies of Met-enkephalin, two extended copies of met-enkephalin, and one copy of leu-enkephalin.^[5] Contrarily, Leu-enkephalin] is predominantly synthesized from prodynorphin, which produces three copies of it per cleavage, and no copies of Met-enkephalin. Other endogenous opioid peptides produced by proenkephalin include adrenorphin,^[6] amidorphin,^[7] BAM-18,^[8] BAM-20P,^[9] BAM-22P,^[9] peptide B,^[10] peptide E,^[11] and peptide F.^[12]

PENK
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1PLW, 1PLX, 2LWC, 5E33, 5E3A
Identifiers
Aliases	PENK, proenkephalin, PE, PENK-A
External IDs	OMIM: 131330; MGI: 104629; HomoloGene: 4528; GeneCards: PENK; OMA:PENK - orthologs
Gene location (Human) Chr. Chromosome 8 (human)[1] Band 8q12.1 Start 56,436,674 bp[1] End 56,446,671 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4 A1|4 2.31 cM Start 4,133,531 bp[2] End 4,138,819 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in nucleus accumbens putamen right testis left testis cartilage tissue caudate nucleus ganglionic eminence middle frontal gyrus external globus pallidus urethra Top expressed in ciliary body olfactory tubercle nucleus accumbens globus pallidus superior frontal gyrus efferent ductule entorhinal cortex calvaria skin of external ear iris More reference expression data BioGPS n/a
Gene ontology Molecular function opioid peptide activity protein binding neuropeptide hormone activity opioid receptor binding Cellular component perikaryon cell body fiber axon symmetric synapse dendrite plasma membrane axon terminus soma extracellular region endoplasmic reticulum lumen synaptic vesicle lumen neuronal dense core vesicle lumen Biological process cellular response to transforming growth factor beta stimulus cellular response to virus general adaptation syndrome, behavioral process response to estradiol response to hypoxia startle response locomotory behavior response to nicotine ageing response to epinephrine cellular response to vitamin D behavioral fear response locomotory exploration behavior response to calcium ion response to morphine response to lipopolysaccharide osteoblast differentiation glial cell proliferation sensory perception of pain cellular response to oxidative stress response to radiation response to ethanol positive regulation of behavioral fear response response to toxic substance cellular response to cAMP aggressive behavior signal transduction sensory perception neuropeptide signaling pathway chemical synaptic transmission post-translational protein modification regulation of signaling receptor activity G protein-coupled receptor signaling pathway response to bacterium Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5179 18619 Ensembl ENSG00000181195 ENSMUSG00000045573 UniProt P01210 P22005 RefSeq (mRNA) NM_006211 NM_001135690 NM_001002927 NM_001348209 RefSeq (protein) NP_001129162 NP_001002927 NP_001335138 Location (UCSC) Chr 8: 56.44 – 56.45 Mb Chr 4: 4.13 – 4.14 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Clinical signficance

Proenkephalin is produced by the medium spiny neurons of the striatum which undergo neurodegeneration in early stages of Huntington's disease (HD). PENK^[13] and related peptides^[14][15] measured in cerebrospinal fluid are proposed as potential biomarkers of disease progression in HD. Furthermore, PENK has been found associated with acute kidney injury^[16] and glomerular filtration rate in steady-state and critically ill patients.^[17][18]

See also

• Prodynorphin (Proenkephalin B)
• Proopiomelanocortin (POMC)

References

1. GRCh38: Ensembl release 89: ENSG00000181195 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000045573 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Donald W. Pfaff (2002). Hormones, brain, and behavior. Elsevier. p. 173. ISBN 978-0-12-532109-9. Retrieved 25 November 2011.
6. Matsuo H, Miyata A, Mizuno K (1983). "Novel C-terminally amidated opioid peptide in human phaeochromocytoma tumour". Nature. 305 (5936): 721–723. Bibcode:1983Natur.305..721M. doi:10.1038/305721a0. PMID 6633641. S2CID 4320171.
7. Seizinger BR, Liebisch DC, Gramsch C, Herz A, Weber E, Evans CJ, et al. (1985). "Isolation and structure of a novel C-terminally amidated opioid peptide, amidorphin, from bovine adrenal medulla". Nature. 313 (5997): 57–59. Bibcode:1985Natur.313...57S. doi:10.1038/313057a0. PMID 3965972. S2CID 4363051.
8. Hurlbut DE, Evans CJ, Barchas JD, Leslie FM (June 1987). "Pharmacological properties of a proenkephalin A-derived opioid peptide: BAM 18". European Journal of Pharmacology. 138 (3): 359–366. doi:10.1016/0014-2999(87)90474-2. PMID 3040439.
9. Mizuno K, Minamino N, Kangawa K, Matsuo H (December 1980). "A new family of endogenous "big" Met-enkephalins from bovine adrenal medulla: purification and structure of docosa- (BAM-22P) and eicosapeptide (BAM-20P) with very potent opiate activity". Biochemical and Biophysical Research Communications. 97 (4): 1283–1290. doi:10.1016/S0006-291X(80)80005-2. PMID 7213356.
10. Micanovic R, Kruggel W, Ray P, Lewis RV (1984). "Purification and sequence of a non-opioid peptide derived from ovine proenkephalin: implications for possible species specific processing". Peptides. 5 (5): 853–856. doi:10.1016/0196-9781(84)90105-0. PMID 6504720. S2CID 3869685.
11. Boarder MR, Evans C, Adams M, Erdelyi E, Barchas JD (December 1987). "Peptide E and its products, BAM 18 and Leu-enkephalin, in bovine adrenal medulla and cultured chromaffin cells: release in response to stimulation". Journal of Neurochemistry. 49 (6): 1824–1832. doi:10.1111/j.1471-4159.1987.tb02443.x. PMID 3681299. S2CID 19919675.
12. Jones BN, Stern AS, Lewis RV, Kimura S, Stein S, Udenfriend S, et al. (October 1980). "Structure of two adrenal polypeptides containing multiple enkephalin sequences". Archives of Biochemistry and Biophysics. 204 (1): 392–395. doi:10.1016/0003-9861(80)90048-X. PMID 7425644.
13. Niemela V, Landtblom AM, Nyholm D, Kneider M, Constantinescu R, Paucar M, et al. (February 2021). "Proenkephalin Decreases in Cerebrospinal Fluid with Symptom Progression of Huntington's Disease". Movement Disorders. 36 (2): 481–491. doi:10.1002/mds.28391. PMC 7984171. PMID 33247616.
14. Iadarola MJ, Mouradian MM (February 1989). "Decrease in a proenkephalin peptide in cerebrospinal fluid in Huntington's disease and progressive supranuclear palsy". Brain Research. 479 (2): 397–401. doi:10.1016/0006-8993(89)91648-X. PMID 2522341. S2CID 11033749.
15. Barschke P, Abu-Rumeileh S, Al Shweiki MH, Barba L, Paolini Paoletti F, Oeckl P, et al. (September 2022). "Cerebrospinal fluid levels of proenkephalin and prodynorphin are differentially altered in Huntington's and Parkinson's disease". Journal of Neurology. 269 (9): 5136–5143. doi:10.1007/s00415-022-11187-8. PMC 9363351. PMID 35737109. S2CID 249930318.
16. Lin LC, Chuan MH, Liu JH, Liao HW, Ng LL, Magnusson M, et al. (December 2023). "Proenkephalin as a biomarker correlates with acute kidney injury: a systematic review with meta-analysis and trial sequential analysis". Critical Care. 27 (1): 481. doi:10.1186/s13054-023-04747-5. PMC 10702091. PMID 38057904.
17. Beunders R, Donato LJ, van Groenendael R, Arlt B, Carvalho-Wodarz C, Schulte J, et al. (November 2023). "Assessing GFR With Proenkephalin". Kidney International Reports. 8 (11): 2345–2355. doi:10.1016/j.ekir.2023.08.006. PMC 10658254. PMID 38025210.
18. Beunders R, van Groenendael R, Leijte GP, Kox M, Pickkers P (September 2020). "Proenkephalin Compared to Conventional Methods to Assess Kidney Function in Critically Ill Sepsis Patients". Shock. 54 (3): 308–314. doi:10.1097/SHK.0000000000001510. PMC 7458088. PMID 31977957.

External links

• Pro-Enkephalin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)